Interferon-Gamma Receptor Signaling Plays an Important Role in Restraining Murine Ovarian Tumor Progression
Bian, Guanglin ; Leigh, Nicholas D LU
; Du, Wei
; Zhang, Lei
; Li, Li
and Cao, Xuefang
(2016)
In Journal of immunology research and therapy
1(1).
p.15-21
- Abstract
Immune cell-derived cytotoxic pathways have been implicated in antitumor immune responses. The goal of this study is to characterize how these cytotoxic pathways influence ovarian cancer development. We have utilized the TgMISIIR-TAg transgenic mouse model which expresses the transforming SV40 TAg in the ovary, leading to spontaneous development of ovarian tumors that closely mimic human epithelial ovarian cancer. To test how perforin (Prf1), granzyme B (GzmB) and interferon-gamma (IFNg) impact tumor occurrence and progression, we bred the TgMISIIR-TAg transgene into Prf1-/-, GzmB-/-, and IFNgR1-/- mice. The transgenic females developed peritoneal tumors at 9-15 weeks and succumbed at 184 ± 37 days of age with 100% penetrance (n=41).... (More)
Immune cell-derived cytotoxic pathways have been implicated in antitumor immune responses. The goal of this study is to characterize how these cytotoxic pathways influence ovarian cancer development. We have utilized the TgMISIIR-TAg transgenic mouse model which expresses the transforming SV40 TAg in the ovary, leading to spontaneous development of ovarian tumors that closely mimic human epithelial ovarian cancer. To test how perforin (Prf1), granzyme B (GzmB) and interferon-gamma (IFNg) impact tumor occurrence and progression, we bred the TgMISIIR-TAg transgene into Prf1-/-, GzmB-/-, and IFNgR1-/- mice. The transgenic females developed peritoneal tumors at 9-15 weeks and succumbed at 184 ± 37 days of age with 100% penetrance (n=41). Knockout of these cytotoxic genes does not affect tumor occurrence. However, loss of function in the IFNg signaling pathway significantly expedited tumor progression with all of the IFNg R1-/- TgMISIIR-TAg females succumbing to tumor outgrowth at 167 ± 27 days of age (p=0.0074, n=24). In contrast, loss of function of Prf1 or GzmB did not significantly impact tumor progression and host survival. Since tumor cells in the IFNg R1-/- TgMISIIR-TAg mice are IFNg R1 deficient, we used the implantable MOSEC (mouse ovarian surface epithelial cell) tumor line to validate that IFNg R signaling in host immune cells but not in tumor cells impacts tumor progression. Indeed, when the IFNg -responsive MOSEC cells were inoculated, IFNg R1-/- mice exhibited significantly higher tumor burden compared to WT mice. Furthermore, a MOSEC-splenocyte co-culture system confirmed that IFNg R1-/- immune cells were less effective than WT immune cells in controlling MOSEC tumor growth in vitro. Together, these results indicate that the IFNg R signaling pathway plays an important role in restraining murine ovarian tumor progression.
(Less)
- author
- Bian, Guanglin
; Leigh, Nicholas D
LU
; Du, Wei
; Zhang, Lei
; Li, Li
and Cao, Xuefang
- publishing date
- 2016-04-28
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology research and therapy
- volume
- 1
- issue
- 1
- pages
- 15 - 21
- publisher
- Hindawi Limited
- external identifiers
-
- pmid:27774523
- ISSN
- 2472-727X
- language
- English
- LU publication?
- no
- id
- d326e31c-b139-44cd-b7ed-eb81e943d035
- date added to LUP
- 2020-04-30 23:10:31
- date last changed
- 2020-05-04 13:37:51
@article{d326e31c-b139-44cd-b7ed-eb81e943d035,
abstract = {{<p>Immune cell-derived cytotoxic pathways have been implicated in antitumor immune responses. The goal of this study is to characterize how these cytotoxic pathways influence ovarian cancer development. We have utilized the TgMISIIR-TAg transgenic mouse model which expresses the transforming SV40 TAg in the ovary, leading to spontaneous development of ovarian tumors that closely mimic human epithelial ovarian cancer. To test how perforin (Prf1), granzyme B (GzmB) and interferon-gamma (IFNg) impact tumor occurrence and progression, we bred the TgMISIIR-TAg transgene into Prf1-/-, GzmB-/-, and IFNgR1-/- mice. The transgenic females developed peritoneal tumors at 9-15 weeks and succumbed at 184 ± 37 days of age with 100% penetrance (n=41). Knockout of these cytotoxic genes does not affect tumor occurrence. However, loss of function in the IFNg signaling pathway significantly expedited tumor progression with all of the IFNg R1-/- TgMISIIR-TAg females succumbing to tumor outgrowth at 167 ± 27 days of age (p=0.0074, n=24). In contrast, loss of function of Prf1 or GzmB did not significantly impact tumor progression and host survival. Since tumor cells in the IFNg R1-/- TgMISIIR-TAg mice are IFNg R1 deficient, we used the implantable MOSEC (mouse ovarian surface epithelial cell) tumor line to validate that IFNg R signaling in host immune cells but not in tumor cells impacts tumor progression. Indeed, when the IFNg -responsive MOSEC cells were inoculated, IFNg R1-/- mice exhibited significantly higher tumor burden compared to WT mice. Furthermore, a MOSEC-splenocyte co-culture system confirmed that IFNg R1-/- immune cells were less effective than WT immune cells in controlling MOSEC tumor growth in vitro. Together, these results indicate that the IFNg R signaling pathway plays an important role in restraining murine ovarian tumor progression.</p>}},
author = {{Bian, Guanglin and Leigh, Nicholas D and Du, Wei and Zhang, Lei and Li, Li and Cao, Xuefang}},
issn = {{2472-727X}},
language = {{eng}},
month = {{04}},
number = {{1}},
pages = {{15--21}},
publisher = {{Hindawi Limited}},
series = {{Journal of immunology research and therapy}},
title = {{Interferon-Gamma Receptor Signaling Plays an Important Role in Restraining Murine Ovarian Tumor Progression}},
url = {{https://lup.lub.lu.se/search/files/79042225/2016_Bian_JIRT.pdf}},
volume = {{1}},
year = {{2016}},
}